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Z. Yao, D. A. West, P. Kuebler, A. Bricarello, J. M. Miller, V. Bantseev, P. E. Miller, T. Nork, L. Damico; Prevention of Laser Photocoagulation Induced Choroidal Neovascularization Lesions by Intravitreal Doses of Ranibizumab in Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2009;50(13):785.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the lowest efficacious ranibizumab dose in cynomolgus monkeys that leads to 100% prevention of laser photocoagulation treatment-induced Grade IV choroidal neovascularization (CNV) lesions.
Cynomolgus monkeys were randomly assigned to two intravitreal dosing regimens. In regimen I, each eye of the animals received one of three doses of ranibizumab (0, 240 and 500 ug/eye) on days 1 and 16. In regimen II, each eye of the animals received one of six doses of ranibizumab (0, 5, 15, 80 and 167 ug/eye) on days 1, 6, 11, 16, 21 and 26. On day 8, the macula of both eyes of all animals underwent laser treatment and nine laser-induced lesions were symmetrically placed in the macula of each eye. Fluorescein angiography was performed on days 29 and 36. Lesions with bright hyperfluorescence early or mid-transit and late leakage beyond borders of the treated area were defined as Grade IV. Serum samples were collected throughout the study. Aqueous humor, vitreous humor and retina tissue were collected at necropsy at day 37. Serum and tissue ranibizumab concentrations were measured.
Serum ranibizumab concentration-time profiles showed biphasic disposition and appeared dose proportional. Ocular tissue ranibizumab concentrations generally were dose proportional. The mean aqueous humor, vitreous humor and retinal concentrations are 47.9, 183 and 156 ng/mL at the lowest dose in regimen I and 18.8, 85.7 and 41.2 ng/mL at the lowest dose in regimen II. In regimen I, 50% of vehicle treated eyes development at least one Grade IV CNV lesion on days 29 and 36. In regimen II, 100% of vehicle treated eyes development at least one Grade IV CNV lesion on days 29 and 36. In both regimens, ranibizumab injections completely prevented the development of Grade IV CNV lesions at all tested dose levels.
Intravitreal injection of ranibizumab at all doses tested and with two dosing regimens completely inhibited the development of Grade IV CNV lesions in the cynomolgus monkey model of laser-induced CNV.
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